Atherosclerosis and cardiovascular disease are leading causes of mortality and morbidity worldwide. Each process can affect major and minor arterial vessels. Yet while arterial and venous thrombosis have numerous origins, it is at the end organs where the effects of the thrombosis are most felt and where those effects result in clinical manifestation. Arterial thrombosis, for example, may manifest as sudden cardiac death, acute coronary syndromes (ACS), stroke, or peripheral embolization. Venous thrombosis may manifest as acute deep vein thrombosis (DVT), pulmonary embolism (PE), or paradoxical arterial embolization.
The underlying causes of these manifestations range from atherosclerosis due to plaque rupture or erosion (e.g., sudden death, ACS, etc), cardiac embolization from atrial fibrillation or left ventricular aneurysm (often secondary to coronary atherosclerosis), stasis and immobility (e.g., postoperative DVT), hypercoagulable state (activated protein C deficiency, malignancy), and a variety of rare disorders. Furthermore, thrombosis may complicate the performance of cardiovascular procedures or initiate malfunction of foreign devices implanted in the cardiovascular system (heart valves, arterial stents, venous filters, bypass grafts, etc).
Given the deleterious impact of atherosclerosis, various interventions have been developed to reduce or remove blockages in blood vessels. One technique for treating stenosis or occlusion of a blood vessel is balloon angioplasty. A balloon catheter is inserted into the narrowed or blocked area, and the balloon is inflated to expand the constricted area. While commonly performed, this method is not without risk. Embolisms can occur during angioplasty when a blocking material dislodges and moves downstream further away of the balloon.
In coronary bypass surgery, a more costly and invasive form of intervention, a section of a vein, such as the saphenous vein taken from the leg, is used to form a connection between the aorta and the coronary artery distal to the obstruction. Over time, however, the saphenous vein graft may itself become diseased, stenosed, or occluded similar to the bypassed vessel. Atherosclerotic plaque in saphenous vein grafts, for example, tends to be more friable and less fibrocalcific than its counterpart in native coronary arteries.
Diffusely diseased saphenous vein grafts with friable atherosclerotic lesions and thrombi have been associated with iatrogenic distal embolic debris. As a result, balloon dilatation (angioplasty) of saphenous vein grafts is more likely to produce symptomatic embolization than dilatation of the coronary arteries. This is the case not only because of the difference in the plaque but also because saphenous vein grafts and their atheromatous plaques are generally larger than the coronary arteries to which they are anastomosed. Once the plaque and thrombi are dislodged from the vein, they can more easily move downstream, completely blocking another portion of the coronary artery and causing myocardial infarction. In fact, coronary embolisms from saphenous vein graft balloon angioplasty are more likely than in native coronary artery balloon angioplasty.
Because of these complications and high recurrence rates, old diffusely diseased saphenous vein grafts have been considered contraindications for standard angioplasty and atherectomy. These complications severely limit the options for minimally invasive treatment, yet the need for intervention remains.
Embolization is also harmful in patients undergoing interventions on the branches of the aortic arch (innominate, carotid, subclavian, vertebral) where the distal embolization may be associated with stroke and devastating neurological deficit. Similarly patients undergoing interventions to the kidney may have embolization and develop renal failure.
Given these limitations, considerable effort has been developed to limit embolization using emboli protection devices. Such devices are well known to those familiar with the art and comprise filters placed distal to the angioplasty site, occlusion devices placed distal to the site, or devices placed proximal to the site.
While these devices are effective at capturing detritus such as large emboli, they may allow small emboli to go across. Further, a reduction in flow across the filter is often noticed when the filter is overwhelmed. Further still, the embolic detritus can directly impact microcirculation and cause impairment of distal organ perfusion.
These complications can lead to myocardial infarction, arrhythmia or death during interventions on the coronary arteries or saphenous vein grafts. They can lead to stroke during interventions on the vessels supplying the brain, renal failure during renal interventions, pulmonary embolism during venous interventions, etc.
These complications are often treated either by administrating therapeutic agents to an angioplasty site or by aspirating columns of blood distal to the angioplasty site. Various agents have been studied for improving cell function and have been administered, in different studies, before or after angioplasty. These agents include beta blockers, adenosine, calcium channel blockers, nitroglycerine, nitroprusside, stem cells, growth factors and combinations thereof. However, given the size of the vessels involved, it is customary to perform angioplasty by removing the angioplasty device, introducing a different catheter, and then administering the therapeutic agent or aspiration. Often this necessitates premature removal of the guidewire, which can preclude access to distal vessels and thus is unpopular. Given the time delay involved with removing the angioplasty device and then inserting the therapeutic or aspiration mechanism, complications may result.
As a result, there is a need for a device that permits delivery of a therapeutic agent distal to the site of angioplasty in a rapid and easy fashion without requiring the removal of the angioplasty device.